Menkes disease is an X-linked lethal multisystem disorder caused by the disturbances of copper distribution in different tissues due to the mutation of ATPA7 gene. The estimated prevalence of the disease is 1 in 100,000 to 1 in 250,000 (Kirodian et al., 2002).

In 1962, Menkes first described the syndrome and Drank et al. noted the association with copper metabolism.[1],[2] The main clinical features include developmental delay, neurological degeneration, and hair abnormalities.[3] Clinical diagnosis can be confirmed by quantifying the serum and urinary levels of copper, serum ceruloplasmin level, and genetic study along with hair changes and radiological findings.[4] We report a classical Menkes disease with characteristic clinical, laboratory, and radiological findings.

Case report

A 9-month-old male child born out of nonconsanguineous marriage was admitted to our hospital with the chief complaints of abnormal movements since 3 months, fever, and difficulty in breathing and feeding since 3 days.

The mother also complained of tremors of the hand, feet, eyelid daily during sleep since last 3 months. On further inquiry, the mother also informed that her baby was lagging in growth and development in comparison to the other children of same age and sex. The child also had an elder sister who had normal growth and development.

On general examination, the baby was conscious, irritable, and afebrile. There was mild pallor, and the skull, spines, and bones were normal. Pulse, blood pressure, and respiratory rate were within normal limits.

Anthropometric measurement showed decrease in head circumference, length, weight, as well as other anthrometric indices suggestive of developmental delay.

On cutaneous examination, the child had fair complexion, chubby cheeks, and depressed nasal bridge. The most striking feature was the scalp hair. The scalp hairs were thin, brittle hair with a metallic grey tone. There was a single circular erythematous patch with scaling and easy pluckable hair suggestive of tinea capitis present on the left side of the scalp. There was absence of signs of primary dentition [Figure 1].

Central nervous system examination revealed that the limbs were hypertonic whereas the trunk was hypotonic. Generalized muscle wasting was present with power grade 3/5 throughout the upper limb and lower limb. Deep tendon reflexes were brisk whereas superficial abdominal reflexes were absent. On auscultation, there were bilateral wheeze and basal crepts. The liver was palpable but the liver span was within normal limit. Gross and fine motor examination revealed that there was no neck holding, sitting with support, pincer grasp, unidextrous, or bidextrous grasp. The child attained social smile at 3 months and recognized his mother at 4 months but was not able to recognize strangers. There was a global developmental delay.

The magnetic resonance imaging (MRI) study of the brain revealed thick subdural collection in bilateral fronto-occipital and temporal area displaying high intensity on t2 intermediate signal intensity on t1wis and flair without diffusion restriction.

Because of the lack of facility, genetic study is not possible in this case. Because copper histidinate or copper acetate is not available, no definite treatment could be performed. The child was treated symptomatically with anticonvulsive drugs, antibiotics for pneumonia, and antifungal for tinea capitis and discharged. The parents were advised for monthly follow-up [Figure 3].

The genetic mutation responsible for the disease was first identified in 1993, leading to a defect in the production of an intracellular protein involved in copper transport.[8],[9]

In Menkes kinky hair disease, the intestinal copper uptake is normal, but copper transport to other tissues is affected. The defective protein is a copper-binding ATPase, ATP7A, and responsible for the distribution and metabolism of copper in tissues. A defect in intestinal copper transport with associated low serum copper and ceruloplasmin levels results in the defective functioning of copper-dependent enzymes such as lysyl oxydase, cytochrome c oxidase, dopamine β-hydroxylase, tyrosinase, and superoxide dismutase with subsequent clinical manifestations. Depigmentation of the hair and skin pallor is due to tyrosinase deficiency, hypothermia is due to cytochrome c oxidase deficiency, lysyl oxidase deficiency causes tortuous arteries in brain, and progressive vascular changes predispose to thrombosis and deficient blood supply to the developing brain.[10],[11],[12] Individuals with Menkes kinky hair disease typically have hypotonia and seizures when they are infants. Although the development initially appears normal, marked developmental delays are noted within the patient’s first year of life. Hair abnormalities are the most striking signs in this syndrome. The scalp hair becomes hypopigmented, sparse, short, and brittle. The skin may become hypopigmented, pale, mottled, and doughy. Examination under microscope reveals a variety of abnormalities, most often pili torti (twisted hair), monilethrix (varying diameter of hair shafts), and trichorrhexis nodosa (fractures of the hair shaft at regular intervals).[13]

X-rays can be helpful in disclosing epiphysary hairlines in the extremities of long bones, whereas bone densitometry can show mild-to-severe osteoporosis in the majority of patients.[4]

MRI abnormalities correspond to neuronal loss and range from isolated cerebral or cerebellar atrophy or both combinations, subdural collections and cerebral hemorrhage.[15],[16],[17]

The treatment options are limited because the brain-blood barrier acts as an obstacle to copper delivery without the transporter protein. In addition, copper is poorly absorbed by the gastrointestinal tract, without attaining an adequate serum level, mainly as copper histidine by parenteral reposition (200–1000 mg/day) might be beneficial in some cases when given early in the course of the disease. There is no evidence, at present, of benefit of parenteral administration of copper associated with D-penicillamine or vitamin E5. The treatment of patients with Menkes disease must also include, when needed, anticonvulsive drugs.[15],[16],[17]

Death usually occurs by the time the individual with Menkes kinky hair disease is aged 3 years, mostly due to respiratory failure.[18] An early diagnosis is important for genetic counseling although no therapy appears effective.[19],[20]

The above case is a very rare genetic disorder, which was first such case in this area. An early diagnosis and management of complication is really important. Parents should be thoroughly counseled about the risks associated with future pregnancy and the importance of prenatal diagnosis so that such pregnancy can be avoided.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Smith VV, Anderson G, Malone M. Light microscopic examination of scalp hair samples as an aid in the diagnosis of pediatric disorders: Retrospective review of more than 300 cases from a single centre. J Clin Pathol 2005;58:1294-8.